Lichen planus (LP) is a chronic debilitating inflammatory disease of unknown etiology affecting the skin, nails, and mucosa with no current FDA-approved treatments. It is histologically characterized by dense infiltration of T cells and epidermal keratinocyte apoptosis. Using global transcriptomic profiling of patient skin samples, we demonstrate that LP is characterized by a type II interferon (IFN) inflammatory response. The type II IFN, IFN-γ, is demonstrated to prime keratinocytes and increase their susceptibility to CD8+ T cell–mediated cytotoxic responses through MHC class I induction in a coculture model. We show that this process is dependent on Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1 (STAT1), but not JAK1 or STAT2 signaling. Last, using drug prediction algorithms, we identify JAK inhibitors as promising therapeutic agents in LP and demonstrate that the JAK1/2 inhibitor baricitinib fully protects keratinocytes against cell-mediated cytotoxic responses in vitro. In summary, this work elucidates the role and mechanisms of IFN-γ in LP pathogenesis and provides evidence for the therapeutic use of JAK inhibitors to limit cell-mediated cytotoxicity in patients with LP.

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle’s disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.

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Background: Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE.Methods: Pathology archives were searched for "SDRIFE" and "baboon syndrome."Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. Results: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." Conclusions: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics. K E Y W O R D S baboon syndrome, drug reaction with eosinophilia and systemic symptoms, histopathology, symmetric drug-related intertriginous and flexural exanthema, toxic erythema of chemotherapy 1 | INTRODUCTION Symmetric drug-related intertriginous and flexural exanthema (SDRIFE) is a rare cutaneous drug reaction characterized clinically by marked erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, symmetric involvement of at least one other intertriginous or flexural area, and the absence of systemic signs or symptoms. 1 It is induced by administration of a systemic agent at first or repeated exposure. 1 Contact allergens should be excluded. Latency between exposure to the offending agent and development of the rash varies but is usually within hours to days. 2

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